Work in the past year has focused on the mechanism of action of the glucocorticoids, the mechanisms of glucocorticoid resistance, the quantitation of glucocorticoid secretion and metabolism in normal and abnormal states, and the mechanisms underlying abnormal 'activation' of the hypothalamic-pituitary-adrenal axis. Results from the years work have shown that glucocorticoid resistance in the New World Primate is associated with mutations in the glucocorticoid receptor in both the steroid binding region and in the region believed to bind heat shock protein. The glucocorticoid resistance found in pituitary tumors secreting ACTH is not associated with any observable mutation in the glucocorticoid receptor. Studies of cortisol production rate in normal subjects and patients with Cushing's Syndrome have demonstrated complete separation of the two groups and have provided a benchmark for the evaluation of the standard tests employed for the diagnosis of Cushing's Syndrome. Finally, a model of depression in a primate has been under study, to elucidate the mechanism underlying activation of the hypothalamic-pituitary-adrenal axis in this disorder. Early results suggest that CRF is necessary for this activation; other requirements are under continued study.